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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #341858
Title: Maternal obesity and gestational weight gain are modestly associated with umbilical cord DNA methylation

Author
item THAKALI, KESHARI - University Arkansas For Medical Sciences (UAMS)
item JENNIFER B FASKE, JENNIFER - University Arkansas For Medical Sciences (UAMS)
item ISHWAR, ARJUN - Agricultural University Of China
item ALFARO, MARIA - Agricultural University Of China
item CLEVES, MARIO - University Arkansas For Medical Sciences (UAMS)
item Badger, Thomas
item ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS)
item SHANKAR, KARTIK - University Arkansas For Medical Sciences (UAMS)

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2017
Publication Date: 7/13/2017
Citation: Thakali, K.M., Jennifer B Faske, J.B., Ishwar, A., Alfaro, M.P., Cleves, M.A., Badger, T.M., Andres, A., Shankar, K. 2017. Maternal obesity and gestational weight gain are modestly associated with umbilical cord DNA methylation. Placenta. Available: https://doi.org/10.1016/j.placenta.2017.07.009.

Interpretive Summary: Obesity in the mother significantly increases the risk of obesity in the child. How this risk is transmitted from mother to child remains unclear. One mechanism via which maternal signals associated with excessive body fat and weight gain in the mother may impact the baby is via changes in the way specific genes are expressed through epigenetic changes. In this study, we examined epigenetic modification of the DNA among genes important in fetal growth and metabolism in umbilical cord tissue collected at birth from 78 infants of normal weight and overweight/obese mothers. Mothers and infants studied were part of the Glowing Study, an ongoing longitudinal study examining the effects of maternal body habitus, diet and metabolism on infant obesity risk. The studies employed a novel technique called bisulfite amplicon sequencing that is able to sequence promoter regions of DNA. This analysis which examined the methylation of DNA showed that infant sex and gestational length influenced the methylation of IGFBP1 and PRKAA1, two genes important in metabolism. Further, maternal BMI influenced the methylation of the non-coding RNA H19 and metabolic regulator PPARGC1A. Maternal obesity also downregulated the protein expression of RAPTOR and AMPK, important in nutrient sensing. These findings provide a novel mechanism via which maternal obesity may persistently affect offspring metabolism and induce developmental programming in the offspring.

Technical Abstract: Maternal obesity (OB) and excessive gestational weight gain (GWG) are strong independent contributors that augment obesity risk in offspring. However, direct evidence of epigenetic changes associated with maternal habitus remains sparse. We utilized Bisulfite Amplicon Sequencing (BSAS) to conduct targeted DNA methylation association analysis of maternal obesity and excessive GWG with DNA methylation of select metabolism-related and imprinted genes. Umbilical cord (UC) tissue from infants born to normal weight and overweight/obese women from the Glowing study were utilized (n=78). In multivariable linear regression adjusted for confounders (maternal early pregnancy BMI (<10 wk pregnancy), gestation length, infant birthweight, and infant fat mass (%) at 2 weeks of age), Institute on Medicine (IOM) GWG category and infant sex were significantly associated with UC IGFBP1 methylation, while gestation length was significantly associated with UC PRKAA1 methylation. In addition, infant fat mass (%) at 2 weeks of age was significantly associated with umbilical cord methylation of RAPTOR. Regression tree analysis confirmed findings from multivariable models demonstrating that maternal early pregnancy BMI and IOM GWG category are important factors in determining fetal UC DNA methylation patterns for select metabolic and imprinted genes. Our findings provide evidence that maternal obesity and excessive GWG have significant effects on the offspring's DNA methylation patterns at birth and provide a mechanistic basis for understanding developmental programming.